Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System

Abstract The cellular behaviors under the control of genetic circuits are subject to stochastic fluctuations, or noise. The stochasticity in gene regulation, far from a nuisance, has been gradually appreciated for its unusual function in cellular activities. In this work, with Chemical Master Equati...

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Autores principales:	Wun-Sin Jhang, Shih-Chiang Lo, Chen-Chao Yeh, Che-Chi Shu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c4682d2d9c7479b825d10b8e0970223
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spelling	oai:doaj.org-article:6c4682d2d9c7479b825d10b8e09702232021-12-02T12:30:26ZInhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System10.1038/s41598-017-04596-72045-2322https://doaj.org/article/6c4682d2d9c7479b825d10b8e09702232017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04596-7https://doaj.org/toc/2045-2322Abstract The cellular behaviors under the control of genetic circuits are subject to stochastic fluctuations, or noise. The stochasticity in gene regulation, far from a nuisance, has been gradually appreciated for its unusual function in cellular activities. In this work, with Chemical Master Equation (CME), we discovered that the addition of inhibitors altered the stochasticity of regulatory proteins. For a bistable system of a mutually inhibitory network, such a change of noise led to the migration of cells in the bimodal distribution. We proposed that the consumption of regulatory protein caused by the addition of inhibitor is not the only reason for pushing cells to the specific state; the change of the intracellular stochasticity is also the main cause for the redistribution. For the level of the inhibitor capable of driving 99% of cells, if there is no consumption of regulatory protein, 88% of cells were guided to the specific state. It implied that cells were pushed, by the inhibitor, to the specific state due to the change of stochasticity.Wun-Sin JhangShih-Chiang LoChen-Chao YehChe-Chi ShuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wun-Sin Jhang Shih-Chiang Lo Chen-Chao Yeh Che-Chi Shu Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System
description	Abstract The cellular behaviors under the control of genetic circuits are subject to stochastic fluctuations, or noise. The stochasticity in gene regulation, far from a nuisance, has been gradually appreciated for its unusual function in cellular activities. In this work, with Chemical Master Equation (CME), we discovered that the addition of inhibitors altered the stochasticity of regulatory proteins. For a bistable system of a mutually inhibitory network, such a change of noise led to the migration of cells in the bimodal distribution. We proposed that the consumption of regulatory protein caused by the addition of inhibitor is not the only reason for pushing cells to the specific state; the change of the intracellular stochasticity is also the main cause for the redistribution. For the level of the inhibitor capable of driving 99% of cells, if there is no consumption of regulatory protein, 88% of cells were guided to the specific state. It implied that cells were pushed, by the inhibitor, to the specific state due to the change of stochasticity.
format	article
author	Wun-Sin Jhang Shih-Chiang Lo Chen-Chao Yeh Che-Chi Shu
author_facet	Wun-Sin Jhang Shih-Chiang Lo Chen-Chao Yeh Che-Chi Shu
author_sort	Wun-Sin Jhang
title	Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System
title_short	Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System
title_full	Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System
title_fullStr	Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System
title_full_unstemmed	Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System
title_sort	inhibitors alter the stochasticity of regulatory proteins to force cells to switch to the other state in the bistable system
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6c4682d2d9c7479b825d10b8e0970223
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_version_	1718394341282545664

Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System

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